management of male infertility - what the future holds
TRANSCRIPT
![Page 1: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/1.jpg)
Sandro Esteves, MD., PhD.
Medical & Scientific Director, ANDROFERT
Campinas, Brazil
Management of Male
Infertility
What the future holds
Reproductive Andrology Surgery Workshop II
Reproductive Medicine Unit - Jahra Hospital - Kuwait 2014
![Page 2: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/2.jpg)
Learning objectives
At the completion of this presentation, participants will have an overview of:
• Sperm biomarkers as diagnostic and treatment tools
• Prospects of male fertility preservation
• Stem cells as new agents for the treatment of male infertility
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 2
2014 December
ANDROFERT
![Page 3: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/3.jpg)
![Page 4: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/4.jpg)
Irvin S, et al 1996, Auger J et al, 1995, Irvine DS 1994, Jørgensen N et al 2001,
Jørgensen N et al 2002, Swan SH 2003, Feki NC et al, 2009
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 5
2014 December
ANDROFERT
![Page 5: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/5.jpg)
Male reproductive relatively simple anatomy hides an overwhelmingly
complex system
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 6
2014 December
ANDROFERT
![Page 6: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/6.jpg)
Spermatogenesis Process
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 7
2014 December
ANDROFERT
![Page 7: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/7.jpg)
Genetic andepigenetic-regulated process
~2,000 genes, but only
30 in the Y
chromosomeHamada et al 2012
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 8
2014 December
ANDROFERT
![Page 8: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/8.jpg)
Extremely specialized cell type
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 9
2014 December
ANDROFERT
![Page 9: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/9.jpg)
Unexplained infertility affects up
to 40% of infertile men
1 in 100 men have no sperm in ejaculate (azoospermia)
Up to 50% aspermatogenic(absolute sterility)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 10
2014 December
ANDROFERT
![Page 10: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/10.jpg)
Limitations of current management
Conventional semen analysis
Conventional surgeries
Empirical medical treatments
ART overuse
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 11
2014 December
ANDROFERT
![Page 11: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/11.jpg)
Recent Advancements
Sperm Function Testing
MicrosurgeryGenetic diagnosis
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 12
2014 December
ANDROFERT
YCMD molecular
diagnosis by PCR
![Page 12: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/12.jpg)
![Page 13: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/13.jpg)
Genomics
Transcriptomics
Proteomics
Metabolomics
The Era of Biomarkers
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 14
2014 December
ANDROFERT
![Page 14: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/14.jpg)
Researchers first to determine entire
genetic sequence of individual sperm
We can look at a
particular individual,
make some calls about
what they would likely
contribute genetically to
an embryo and perhaps
even diagnose or detect
potential problems, and
identify healthy sperm
for use in IVF
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 15
2014 December
ANDROFERT
![Page 15: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/15.jpg)
Normalcy of Sperm Chromatin Content
DNA Micro-array Technology
• Glass or silicon slides
where thousands of
features are arrayed
• Gene expression is
measured hybridization
process
• Microarrays are read using
laser-based fluorescence
scanners
• Determine which genes are
active and at what levels
• Compare with controls, etc.
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 16
2014 December
ANDROFERT
![Page 16: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/16.jpg)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 17
2014 December
ANDROFERT
![Page 17: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/17.jpg)
Potential Clinical Applications of Sperm Molecular Genetic
Fingerprinting
• Infertility diagnosis
• Assessment of treatment outcome (medical, surgical)
• ART outcome (IUI, IVF, ICSI)
• Sperm selection techniques
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 18
2014 December
ANDROFERT
![Page 18: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/18.jpg)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 19
2014 December
ANDROFERT
Seminal Fluid Molecular Genetic Fingerprinting
![Page 19: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/19.jpg)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 20
2014 December
ANDROFERT
![Page 20: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/20.jpg)
Proteins are also critical to understanding disease
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 21
2014 December
ANDROFERT
![Page 21: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/21.jpg)
Proteomics
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 22
2014 December
ANDROFERT
Mass Spectroscopy
Raman Spectroscopy
Nuclear Magnetic
Resonance
![Page 22: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/22.jpg)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 23
2014 December
ANDROFERT
![Page 23: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/23.jpg)
Sperm & Seminal Plasma Proteomic Profiles
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 24
2014 December
ANDROFERT
![Page 24: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/24.jpg)
Sp
erm
P
rote
om
ics
![Page 25: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/25.jpg)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 26
2014 December
ANDROFERTCamargo M et al. Hum. Reprod. 2013;28:33-46
Change in proteomic profiling in seminal plasma of adult men before and after
varicocelectomy
![Page 26: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/26.jpg)
![Page 27: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/27.jpg)
Sperm,
spermatids
Embryos
Oocytes
Ovarian tissue
?Male germ cells
?Testicular
tissue
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 28
2014 December
ANDROFERT
![Page 28: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/28.jpg)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 29
2014 December
ANDROFERT
![Page 29: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/29.jpg)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 30
2014 December
ANDROFERT
![Page 30: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/30.jpg)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 31
2014 December
ANDROFERT
![Page 31: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/31.jpg)
Spermatogonial stem cell preservation and transplantation
• Boys facing gonadotropic treatment
• Klinefelter syndrome patientsCryopreservation before SSC loss
• Extraction: testicular biopsy
• Freezing : slow-freezing and storage of testicular
tissue or cell suspension in LN
• Cryoprotectant: DMSO
• Grafting: ectopic or homotopic (mouse)
• When to graft: unknown
• Fertilizing capacity in humans: unknown
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 32
2014 December
ANDROFERT
![Page 32: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/32.jpg)
![Page 33: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/33.jpg)
Nonobstructive azoospermia irreversible condition
Testicular torsion; Trauma
Post-inflammatory (eg. Mumps orchitis)
Exogenous factors (eg. Cytotoxic drugs, irradiation)
Testicular cancer
Systemic diseases (eg. Liver cirrhosis, renal failure)
Congenital
Testicular dysgenesis/cryptorchidism
Genetic abnormalities (Klinefelter syndrome, Yq microdeletions, etc.)
Acquired
Idiopathic (Unknown etiology)
Esteves et al. Clinics 2011; 66: 691-700
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 34
2014 December
ANDROFERT
![Page 34: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/34.jpg)
Current method for identification of sperm production sites in nonobstructive
azoospermia
Esteves et al Int Braz J Urol 2013; 37: 570-83; Deruyver et al Andrology 2014; 2: 20-4
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 35
2014 December
ANDROFERT
![Page 35: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/35.jpg)
Morphometric Evaluation of Seminiferous Tubules
Median 25%-75% 5%-95% Raw Data
yes No
Presence of Sperm
160
180
200
220
240
260
280
300
320
340
360
380
400
420
Max.
Tubule
Dia
mete
r
Verza Jr S, Esteves SC. Fertil Steril 2012; 98: S242
N=54; Tubule Diameter: KW-H (1;54) = 25.2; P<0.001
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 36
2014 December
ANDROFERT
![Page 36: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/36.jpg)
Novel methods for identification of sperm production sites in men with nonobstructive
azoospermia
Multi-photon microscopy(ex vivo; human model)
Confocal fluorescence microscopy
(in vivo; murine model)
Full-field optical coherence tomography
(ex vivo; rat model)
Najari et al, J Urol 2012; Smith et al J Urol 2012; Ramasamy et al., J Pathol Inform 2012
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 37
2014 December
ANDROFERT
![Page 37: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/37.jpg)
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 38
2014 December
ANDROFERT
No residual sperm production in up to 50% of men with NOA
![Page 38: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/38.jpg)
In mice, transplanted stem cell-derived male gametes resulted in
proper spermatogenesis
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 39
2014 December
ANDROFERT
![Page 39: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/39.jpg)
In mice, derived gametes generate viable offspring
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 40
2014 December
ANDROFERTAponte et al, Clinics 2013
![Page 40: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/40.jpg)
Biotechnological advancements in the treatment of aspermatogenic men
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 41
2014 December
ANDROFERT
![Page 41: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/41.jpg)
Conclusions
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 42
2014 December
ANDROFERT
• Novel genomic and proteomic biomarkers could add to work-up and clinical treatment strategies
• Advances in immature germ cells cryopreservation/transplantation will expand fertility options for oncological boys
• Biotechnological approaches for generating male gametes last frontier to be accomplished
![Page 42: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/42.jpg)
Why we should do all that …
Courtesy of E.N. & T.A.S. with permission
ANDROFERTandrofert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 43
2014 December
ANDROFERT
![Page 43: Management of Male Infertility - What the future holds](https://reader033.vdocument.in/reader033/viewer/2022052912/55a13ede1a28abe4278b460e/html5/thumbnails/43.jpg)